Recent Publications and Allostery Project

Jens Kleinjung
03.10.2017

1. Blastocyst

Genome editing reveals a role for OCT4 in human embryogenesis.
Fogarty, ..., Niakan (Sep. 2017) Nature.


An engineered photoswitchable mammalian pyruvate kinase.
Gehrig, ..., Anastasiou et al.(2017) The FEBS Journal.

Chimera with Light-oxygen-voltage-sensing Domain

Light-modulated Enzymatic Activity

3. Fragments: The M32K25 Structural Alphabet

Symbolic Abstraction

Attractors in Conformational Space

  • Clearly defined attractors
  • Local energy minima
  • Protein structure is assembly of local energy minima
  • Structural sequences as new abstraction layer

Canonical Fragments

alt text

  • 25 canonical C\( _4^{\alpha} \) fragments
  • Fit quality: 0.70-1.00 Ã… RMSD for global fit (superimposed ends)
  • Encoding of dynamics: Correlation >0.7 between RMSF and H\( _{Shannon} \)(M32K25)

Structural alphabets derived from attractors in conformational space.
Pandini, Kleinjung et al., BMC Bioinformatics 11 (2010) 97.

Fragment Fit

alt text

\[ RMSF = \sqrt{\langle r^2 \rangle - \langle r \rangle ^2} \]

...WUWVURPNMUVWVVUUUW...
...UUUVXTOTSUWUUUVWVW...
...VUTVXRJUQXVUUVWTWV...
...VWUVXTFQQUWXUUVUUU...
...XXTUWSOTRUWVUUVWUU...
...XXTWXROUSUUUUUUUWU...

\[ H_{Shannon} = - \sum p_i \; log \; p_i \]

4. Analysis of Allosteric Signal Transmission

GSATools: analysis of allosteric communication and functional local motions in GROMACS using a Structural Alphabet.
Pandini et al., Bioinformatics 29 (2013) 2053–2055.

Allostery in NtrC

PKM2 Long-range Couplings

See also:
An engineered photoswitchable mammalian pyruvate kinase.
Gehrig et al., FEBS J. (2017) 14175.

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